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1.
J Infect Chemother ; 25(6): 413-422, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30905628

RESUMO

The Japanese Surveillance Committee conducted a second nationwide surveillance of antimicrobial susceptibility patterns of uropathogens responsible for acute uncomplicated cystitis (AUC) in premenopausal patients aged 16-40 years old at 31 hospitals throughout Japan from March 2015 to February 2016. In this study, the susceptibility of causative bacteria (Escherichia coli, Klebsiella pneumoniae, Staphylococcus saprophyticus) for various antimicrobial agents was investigated by isolation and culturing of organisms obtained from urine samples. In total, 324 strains were isolated from 361 patients, including E. coli (n = 220, 67.9%), S. saprophyticus (n = 36, 11.1%), and K. pneumoniae (n = 7, 2.2%). The minimum inhibitory concentrations (MICs) of 20 antibacterial agents for these strains were determined according to the Clinical and Laboratory Standards Institute (CLSI) manual. At least 93% of the E. coli isolates showed susceptibility to fluoroquinolones and cephalosporins, whereas 100% of the S. saprophyticus isolates showed susceptibility to fluoroquinolones and aminoglycosides. The proportions of fluoroquinolone-resistant and extended-spectrum ß-lactamase (ESBL)-producing E. coli strains were 6.4% (13/220) and 4.1% (9/220), respectively. The antimicrobial susceptibility of K. pneumoniae was retained during the surveillance period, while no multidrug-resistant strains were identified. In summary, antimicrobial susceptibility results of our second nationwide surveillance did not differ significantly from those of the first surveillance. Especially the numbers of fluoroquinolone-resistant and ESBL-producing E. coli strains were not increased in premenopausal patients with AUC in Japan.


Assuntos
Antibacterianos/farmacologia , Cistite/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla , Escherichia coli/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Staphylococcus saprophyticus/efeitos dos fármacos , Adolescente , Adulto , Antibacterianos/uso terapêutico , Cistite/epidemiologia , Cistite/microbiologia , Monitoramento Epidemiológico , Escherichia coli/isolamento & purificação , Escherichia coli/metabolismo , Feminino , Humanos , Japão , Klebsiella pneumoniae/isolamento & purificação , Klebsiella pneumoniae/metabolismo , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Staphylococcus saprophyticus/isolamento & purificação , Staphylococcus saprophyticus/metabolismo , Adulto Jovem , beta-Lactamases/metabolismo
2.
J Infect Chemother ; 25(2): 104-110, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30420153

RESUMO

We report efficacy and safety results for a combination of a novel cephalosporin class antibiotic and a ß-Lactamase inhibitor, tazobactam/ceftolozane (1:2) at a dose of 1.5 g intravenously every 8 h in Japanese patients with uncomplicated pyelonephritis and complicated urinary tract infection. This study design was a nonrandomized, multicenter, open-label trial, and the treatment period was 7 days. Of 115 patients enrolled in this study, 114 received tazobactam/ceftolozane, and 90 were included in the efficacy analyses. Ninety-nine isolates (bacterial count ≥105 CFU/mL) were identified by urine culture. The main baseline uropathogens were Escherichia coli (80 isolates), Klebsiella pneumoniae (8 isolates), and Proteus mirabilis (3 isolates). Of these, 13 isolates were ESBL-producers. The favorable per-patient microbiological response rate at 7 days after the final administration of tazobactam/ceftolozane was 80.7% (71/88). The response rate in uncomplicated pyelonephritis was 90.0% (36/40), complicated pyelonephritis 63.6% (14/22), and complicated cystitis 80.8% (21/26). The favorable clinical response rate was 96.6% (86/89), and composite response rate (based on microbiological and clinical response) was 80.7% (71/88). The eradication rate by uropathogen was 83.5% (66/79) in E. coli, 42.9% (3/7) in K. pneumoniae, and 100% (3/3) in P. mirabilis. The incidence of drug-related adverse events was 17.5% (20/114 patients). The most common drug-related adverse events were diarrhea and alanine aminotransferase increased in 5.3% (6/114 patients each). Drug-related serious adverse events and deaths were not observed. These results support the safety and efficacy of tazobactam/ceftolozane and suggest it will be a useful treatment for uncomplicated pyelonephritis and complicated urinary tract infection.


Assuntos
Antibacterianos/efeitos adversos , Cefalosporinas/efeitos adversos , Pielonefrite/tratamento farmacológico , Tazobactam/efeitos adversos , Infecções Urinárias/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Tazobactam/uso terapêutico , Resultado do Tratamento
3.
J Infect Chemother ; 22(9): 581-6, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27452428

RESUMO

Genital chlamydial infection is a principal sexually transmitted infection worldwide. Chlamydia trachomatis can cause male urethritis, acute epididymitis, cervicitis, and pelvic inflammatory disease as sexually transmitted infections. Fortunately, homotypic resistant C. trachomatis strains have not been isolated to date; however, several studies have reported the isolation of heterotypic resistant strains from patients. In this surveillance study, clinical urethral discharge specimens were collected from patients with urethritis in 51 hospitals and clinics in 2009 and 38 in 2012. Based on serial cultures, the minimum inhibitory concentration (MIC) could be determined for 19 isolates in 2009 and 39 in 2012. In 2009 and 2012, the MICs (MIC90) of ciprofloxacin, levofloxacin, tosufloxacin, sitafloxacin, doxycycline, minocycline, erythromycin, clarithromycin, and azithromycin were 2 µg/ml and 1 µg/ml, 0.5 µg/ml and 0.5 µg/ml, 0.125 µg/ml and 0.125 µg/ml, 0.063 µg/ml and 0.063 µg/ml, 0.125 µg/ml and 0.125 µg/ml, 0.125 µg/ml and 0.125 µg/ml, 0.016 µg/ml and 0.016 µg/ml, and 0.063 µg/ml and 0.063 µg/ml, respectively. In summary, this surveillance project did not identify any resistant strain against fluoroquinolone, tetracycline, or macrolide agents in Japan.


Assuntos
Antibacterianos/farmacologia , Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis/efeitos dos fármacos , Farmacorresistência Bacteriana , Fluoroquinolonas/farmacologia , Adolescente , Adulto , Técnicas de Cultura de Células , Infecções por Chlamydia/transmissão , Chlamydia trachomatis/isolamento & purificação , Humanos , Japão/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Vigilância em Saúde Pública , Uretrite/microbiologia , Adulto Jovem
4.
J Infect Chemother ; 21(5): 340-5, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25727286

RESUMO

Worldwide, the most important concern in the treatment of sexually transmitted infections is the increase in antimicrobial resistant Neisseria gonorrhoeae strains including resistance to cephalosporins, penicillins, fluoroquinolones or macrolides. To investigate the trends of antimicrobial susceptibility among N. gonorrhoeae strains isolated from male patients with urethritis, a Japanese surveillance committee conducted the second nationwide surveillance study. Urethral discharge was collected from male patients with urethritis at 26 medical facilities from March 2012 to January 2013. Of the 151 specimens, 103 N. gonorrhoeae strains were tested for susceptibility to 20 antimicrobial agents. None of the strains was resistant to ceftriaxone, but the minimum inhibitory concentration (MIC) 90% of ceftriaxone increased to 0.125 µg/ml, and 11 (10.7%) strains were considered less susceptible with an MIC of 0.125 µg/ml. There were 11 strains resistant to cefixime, and the MICs of these strains were 0.5 µg/ml. The distributions of the MICs of fluoroquinolones, such as ciprofloxacin, levofloxacin and tosufloxacin, were bimodal. Sitafloxacin, a fluoroquinolone, showed strong activity against all strains, including strains resistant to other three fluoroquinolones, such as ciprofloxacin, levofloxacin and tosufloxacin. The azithromycin MICs in 2 strains were 1 µg/ml.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Neisseria gonorrhoeae/efeitos dos fármacos , Vigilância da População , Uretrite/microbiologia , Adolescente , Adulto , Idoso , Azitromicina/farmacologia , Cefixima/farmacologia , Ceftriaxona/farmacologia , Fluoroquinolonas/farmacologia , Humanos , Japão , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Penicilinas/farmacologia , Adulto Jovem
5.
Int J Urol ; 19(4): 360-8, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22211478

RESUMO

OBJECTIVES: Coincident with their worldwide use, resistance to fluoroquinolones in Escherichia coli has increased. To identify the gene expression profiles underlying fluoroquinolone resistance, we carried out genome-wide transcriptome analysis of fluoroquinolone-sensitive E. coli. METHODS: Four fluoroquinolone-sensitive E. coli and five fluoroquinolone-resistant E. coli clinical isolates were subjected to complementary deoxyribonucleic acid microarray analysis. Some upregulated genes' expression was verified by real-time polymerase chain reaction using 104 E. coli clinical isolates, and minimum inhibitory concentration tests were carried out by using their transformants. RESULTS: A total of 40 genes were significantly upregulated in fluoroquinolone-resistant E. coli isolates (P < 0.05). The expression of phage shock protein operons, which are involved in biofilm formation, was markedly upregulated in our profile of fluoroquinolone-resistant E. coli. One of the phage shock protein operons, pspC, was significantly upregulated in 50 fluoroquinolone-resistant E. coli isolates (P < 0.0001). The expression of type I fimbriae genes, which are pilus operons involved in biofilm formation, were markedly downregulated in fluoroquinolone-resistant E. coli. Deoxyribonucleic acid adenine methyltransferase (dam), which represses type I fimbriae genes, was significantly upregulated in the clinical fluoroquinolone-resistant E. coli isolates (P = 0.007). We established pspC- and dam-expressing E. coli transformants from fluoroquinolone-sensitive E. coli, and the minimum inhibitory concentration tests showed that the transformants acquired fluoroquinolone resistance, suggesting that upregulation of these genes contributes to acquiring fluoroquinolone resistance. CONCLUSIONS: Upregulation of psp operones and dam underlying pilus operons downregulation might be associated with fluoroquinolone resistance in E. coli.


Assuntos
Antibacterianos/farmacologia , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Fluoroquinolonas/farmacologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Ciprofloxacino/farmacologia , Ciprofloxacino/uso terapêutico , Farmacorresistência Bacteriana/genética , Feminino , Fluoroquinolonas/uso terapêutico , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Genoma Bacteriano , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Ofloxacino/farmacologia , Ofloxacino/uso terapêutico , Transcriptoma , Adulto Jovem
6.
Jpn J Antibiot ; 59(1): 21-8, 2006 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-16673579

RESUMO

Using the agar dilution method, the antibacterial activity of 18 antibiotics inclusive of 4 carbapenems were investigated against 101 strains of urinary pathogens isolated from patients with urinary tract infections who visited the Department of Urology at Kagoshima University Hospital, between January and December 2002. 4 strains of Staphylococcus aureus, 3 strains of Staphylococcus spp. (exclusive of S. aureus), 14 strains of Enterococcus faecalis, 3 strains of Enterococcus spp. (exclusive of E. faecalis), 41 strains of Escherichia coli, 21 strains of Enterobacteriaceae (exclusive of E. coli), 12 strains of Pseudomonas aeruginosa and 3 strains of glucose-nonfermentative Gram-negative rods (exclusive of P. aeruginosa) were examined. 1. Against clinical isolates of Gram-positive bacteria, vancomycin and teicoplanin were active. Additionally, arbekacin was active against S. aureus clinical isolates and ampicillin was active against E. faecalis clinical isolates. Carbapenems were active against clinical isolates of Gram-positive bacteria, except for multi-drug resistant strains of Gram-positive bacteria, such as methicillin-resistant S. aureus. 2. As for clinical isolates of Gram-negative bacteria, meropenem was most active against Enterobacteriaceae among 13 antibiotics tested. Against P. aeruginosa clinical isolates, MIC90 of meropenem was the lowest among 13 antibiotics tested. In addition, resistant rate of meropenem and biapenem against P. aeruginosa clinical isolates was lower than those of the other carbapenems tested. 3. As main urinary pathogens showed no remarkable increase in resistance to carbapenems, it can be stated that carbapenems retain their position as the drug of first choice for severe infection.


Assuntos
Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Bactérias Gram-Positivas/efeitos dos fármacos , Infecções Urinárias/microbiologia , Farmacorresistência Bacteriana , Enterobacteriaceae/efeitos dos fármacos , Enterococcus/efeitos dos fármacos , Enterococcus faecalis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Humanos , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
7.
Int J Mol Med ; 17(6): 1085-91, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16685420

RESUMO

Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor (PD-ECGF), has been implicated in bladder cancer angiogenesis and invasion. However, the molecular basis of its role in invasion remains unclear. We investigated the expression of TP and 10 invasion-related genes in bladder cancers from 72 randomly selected patients by real-time two-step RT-PCR assay. We found that the expression levels of TP, MMP-9, uPA, and MMP-2 were significantly higher in invasive tumors than those in superficial tumors. Also, the expression level of TP significantly correlated with that of uPA, MMP-1, MMP-9, PAI-1 and VEGF. KK47/TP cells, bladder cancer cells that overexpress TP, had a higher expression of MMP-7 and MMP-9 than KK/CV cells that express lower level of TP in hypoxic condition. PC/TP cells, prostate cancer cells that overexpress TP, also had a higher expression of MMP-1 and MMP-7 than PC/CV cells that express no detectable TP. Taken together these data indicate that TP enhances the invasion of tumor cells through the induction of invasion-related genes.


Assuntos
Regulação Neoplásica da Expressão Gênica , Invasividade Neoplásica/genética , Timidina Fosforilase/genética , Ativação Transcricional , Neoplasias da Bexiga Urinária/enzimologia , Neoplasias da Bexiga Urinária/patologia , Linhagem Celular Tumoral , Feminino , Genes Neoplásicos , Humanos , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Bexiga Urinária/genética , Ativador de Plasminogênio Tipo Uroquinase/genética
8.
Biochem Biophys Res Commun ; 339(3): 790-6, 2006 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-16316628

RESUMO

Promoter hypermethylation is one of the putative mechanisms underlying the inactivation of negative cell-cycle regulators. We examined whether the methylation status of p16(INK4a) and p14(ARF), genes located upstream of the RB and p53 pathway, is a useful biomarker for the staging, clinical outcome, and prognosis of human bladder cancer. Using methylation-specific PCR (MSP), we examined the methylation status of p16(INK4a) and p14(ARF) in 64 samples from 45 bladder cancer patients (34 males, 11 females). In 19 patients with recurrent bladder cancer, we examined paired tissue samples from their primary and recurrent tumors. The methylation status of representative samples was confirmed by bisulfite DNA sequencing analysis. The median follow-up duration was 34.3 months (range 27.0-100.1 months). The methylation rate for p16(INK4a) and p14(ARF) was 17.8% and 31.1%, respectively, in the 45 patients. The incidence of p16(INKa) and p14(ARF) methylation was significantly higher in patients with invasive (>or=pT2) than superficial bladder cancer (pT1) (p=0.006 and p=0.001, respectively). No MSP bands for p16(INK4a) and p14(ARF) were detected in the 8 patients with superficial, non-recurrent tumors. In 19 patients with tumor recurrence, the p16(INK4a) and p14(ARF) methylation status of the primary and recurrent tumors was similar. Of the 22 patients who had undergone cystectomy, 8 (36.4%) manifested p16(INKa) methylation; p16(INK4a) was not methylated in 23 patients without cystectomy (p=0.002). Kaplan-Meier analysis revealed that patients with p14(ARF) methylation had a significantly poorer prognosis than those without (p=0.029). This is the first study indicating that MSP analysis of p16(INK4a) and p14(ARF) genes is a useful biomarker for the pathological stage, clinical outcome, and prognosis of patients with bladder cancer.


Assuntos
Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/genética , Análise Mutacional de DNA/métodos , Proteína Supressora de Tumor p14ARF/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Idoso , Idoso de 80 Anos ou mais , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Metilação de DNA , DNA de Neoplasias/análise , DNA de Neoplasias/genética , Estudos de Viabilidade , Feminino , Testes Genéticos/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Proteína Supressora de Tumor p14ARF/metabolismo , Neoplasias da Bexiga Urinária/diagnóstico
9.
Cancer ; 106(1): 79-86, 2006 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-16323173

RESUMO

BACKGROUND: Aberrant CpG methylation profiles of gene promoters and their correlation with advanced pathologic features have been well investigated in prostate carcinoma (PC). Several case-control and prospective studies have revealed a positive association between current smoking and PC. The authors hypothesized that smoking influences both progression and prognosis of PC through CpG hypermethylation of related genes. METHODS: A total of 164 PC patients (52 current, 30 former, and 82 never smokers) and 69 benign prostatic hyperplasia (BPH) patients were examined by methylation-specific PCR (MSP) for 3 genes: adenomatous polyposis coli (APC), glutathione S-transferase pi (GSTP1), and multidrug resistance one (MDR1). The methylation status of representative samples was confirmed by bisulfite DNA sequencing analysis. The newly defined methylation score (M-score) of each sample is the sum of the corresponding log hazard ratio (HR) coefficients derived from multivariate logistic regression analysis for pathology (BPH vs. PC), and was related to clinical and pathologic outcome including smoking status. RESULTS: The M-score was significantly higher in the current smokers than in never smokers (P = 0.008). Spearman rank correlation test demonstrated a significant correlation between pack-years smoked and M-score in PCs (P = 0.039). Significant correlation of the M-score methylation was observed with high pT category (P < 0.001), high Gleason sum (P < 0.001), high preoperative prostate-specific antigen (PSA) (P = 0.041), and advanced pathologic features. In addition, Gleason sum was significantly associated with PSA failure-free probability as a poor outcome (P = 0.020). CONCLUSIONS: This is the first study to demonstrate significant correlation of the methylation status of multigenes with smoking status in PC. Smoking status may influence both progression and prognosis of PC through CpG hypermethylation of related genes.


Assuntos
Ilhas de CpG , Metilação de DNA , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/metabolismo , Fumar/efeitos adversos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Proteína da Polipose Adenomatosa do Colo/genética , Proteína da Polipose Adenomatosa do Colo/metabolismo , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Glutationa S-Transferase pi/genética , Glutationa S-Transferase pi/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Regiões Promotoras Genéticas , Hiperplasia Prostática/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Análise de Regressão
10.
Clin Cancer Res ; 11(18): 6582-8, 2005 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-16166436

RESUMO

PURPOSE: Aberrant gene promoter methylation profiles have been well-studied in human prostate cancer. Therefore, we rationalize that multigene methylation analysis could be useful as a diagnostic biomarker. We hypothesize that a new method of multigene methylation analysis could be a good diagnostic and staging biomarker for prostate cancer. EXPERIMENTAL DESIGN: To test our hypothesis, prostate cancer samples (170) and benign prostatic hyperplasia samples (69) were examined by methylation-specific PCR for three genes: adenomatous polyposis coli (APC), glutathione S-transferase pi (GSTP1), and multidrug resistance 1 (MDR1). The methylation status of representative samples was confirmed by bisulfite DNA sequencing analysis. We further investigated whether methylation score (M score) can be used as a diagnostic and staging biomarker for prostate cancer. The M score of each sample was calculated as the sum of the corresponding log hazard ratio coefficients derived from multivariate logistic regression analysis of methylation status of various genes for benign prostatic hyperplasia and prostate cancer. The optimal sensitivity and specificity of the M score for diagnosis and for staging of prostate cancer was determined by receiver-operator characteristic (ROC) curve analysis. A pairwise comparison was employed to test for significance using the area under the ROC curve analysis. For each clinicopathologic finding, the association with prostate-specific antigen (PSA) failure-free probability was determined using Kaplan-Meier curves and a log-rank test was used to determine significance. The relationship between M score and clinicopathologic findings was analyzed by either the Mann-Whitney U test, Kruskal-Wallis test, or the Spearman rank correlation test. RESULTS: The frequency of positive methylation-specific PCR bands for APC, GSTP1, and MDR1 genes in prostate cancer samples was 64.1%, 54.0%, and 55.3%, respectively. In benign prostatic hyperplasia samples, it was 8.7%, 5.8%, and 11.6%, respectively. There was a significant correlation of M score with high pT category (P < 0.001), high Gleason sum (P < 0.001), high preoperative PSA (P = 0.027), and advanced pathologic features. For all patients, the M score had a sensitivity of 75.9% and a specificity of 84.1% as a diagnostic biomarker using a cutoff value of 1.0. In patients with low or borderline PSA levels (<10.0 ng/mL), the M score was significantly higher in prostate cancers than in benign prostatic hyperplasias (2.635 +/- 0.200 and 0.357 +/- 0.121, respectively). ROC curve analysis revealed that the M score had a sensitivity of 65.4% and a specificity of 94.2% when 1.0 was used as a cutoff value. For all patients, M score can distinguish organ-confined (< or =pT(2)) from locally advanced cancer (> or =pT(3)) with a sensitivity of 72.1% and a specificity of 67.8%. Moreover, considering patients with PSA levels of <10 ng/mL, the M score has a sensitivity of 67.1% and a specificity of 85.7%. The ROC curve analysis showed a significant difference between M score and PSA (P = 0.010). CONCLUSIONS: This is the first report demonstrating that M score is a new method for multigene methylation analysis that can serve as a good diagnostic and staging biomarker for prostate cancer.


Assuntos
Metilação de DNA , Estadiamento de Neoplasias/métodos , Neoplasias da Próstata/patologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Proteína da Polipose Adenomatosa do Colo/genética , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Glutationa S-Transferase pi , Glutationa Transferase/genética , Humanos , Isoenzimas/genética , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/sangue , Hiperplasia Prostática/genética , Hiperplasia Prostática/patologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/genética , Reprodutibilidade dos Testes
11.
Int J Cancer ; 116(2): 174-81, 2005 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-15800905

RESUMO

The incidence and mortality of prostate cancer (PC) is approximately 2-fold higher among African-Americans as compared to Caucasians and very low in Asian. We hypothesize that inactivation of GSTP1 genes through CpG methylation plays a role in the pathogenesis of PC, and its ability to serve as a diagnostic marker that differs among ethnic groups. GSTP1 promoter hypermethylation and its correlation with clinico-pathological findings were evaluated in 291 PC (Asian = 170; African-American = 44; Caucasian = 77) and 172 benign prostate hypertrophy samples (BPH) (Asian = 96; African-American = 38; Caucasian = 38) using methylation-specific PCR. In PC cells, 5-aza-dC treatment increased expression of GSTP1 mRNA transcripts. The methylation of all CpG sites was found in 191 of 291 PC (65.6%), but only in 34 of 139 BPH (24.5%). The GSTP1 hypermethylation was significantly higher in PC as compared to BPH in each ethnic group (p < 0.0001). Logistic regression analysis (PC vs. BPH) showed that African-Americans had a higher hazard ratio (HR) (13.361) compared to Caucasians (3.829) and Asian (8.603). Chi-square analysis showed correlation of GSTP1 hypermethylation with pathological findings (pT categories and higher Gleason sum) in Asian PC (p < 0.0001) but not in African-Americans and Caucasian PC. Our results suggest that GSTP1 hypermethylation is a sensitive biomarker in African-Americans as compared to that in Caucasians or Asian, and that it strongly influences tumor progression in Asian PC. Ours is the first study investigating GSTP1 methylation differences in PC among African-American, Caucasian and Asian.


Assuntos
Afro-Americanos , Grupo com Ancestrais do Continente Asiático , Ilhas de CpG/genética , Metilação de DNA , Grupo com Ancestrais do Continente Europeu , Glutationa Transferase/genética , Glutationa Transferase/fisiologia , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Hiperplasia Prostática/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
12.
Cancer Res ; 64(17): 5956-62, 2004 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-15342374

RESUMO

Multidrug resistance 1 (MDR1) gene encodes for P-glycoprotein (P-gp), a Mr 170,000 transmembrane calcium-dependent efflux pump that is inactivated in prostate cancer. We hypothesize that inactivation of the MDR1 gene through CpG methylation contributes to the pathogenesis and progression of prostate cancer. To test this hypothesis, CpG methylation status of the MDR1 promoter and its correlation with clinicopathological findings were evaluated in 177 prostate cancer samples and 69 benign prostate hypertrophy (BPH) samples. Cellular proliferation index and apoptotic index were determined by proliferating cell nuclear antigen (PCNA) and single-strand DNA immunostaining, respectively. After 5-aza-2'-deoxycytidine treatment, increased expression of MDR1 mRNA transcript was found in prostate cancer cell lines (DU145, DuPro, and ND1). MDR1 methylation frequency was significantly higher in prostate cancer samples compared with BPH samples (54.8 versus 11.6%, respectively, P < 0.001). Logistic regression analysis revealed that PC patients are 11.5 times more likely to have MDR1 methylation than BPH patients (95% confidence interval 4.87-27.0) and that MDR1 methylation is independent of the age. Significant correlation of MDR1 methylation was observed with high pT category (P < 0.001), high Gleason sum (P = 0.008), high preoperative prostate-specific antigen (P = 0.01), and advancing pathological features. In addition, PCNA-labeling index were significantly higher in methylation-specific PCR (MSP)-positive than in MSP-negative prostate cancer samples (P = 0.048). In contrast, no significant difference in apoptotic index was found between MSP-positive and -negative prostate cancer samples. These findings suggest that CpG hypermethylation of MDR1 promoter is a frequent event in prostate cancer and is related to disease progression via increased cell proliferation in prostate cancer cells.


Assuntos
Azacitidina/análogos & derivados , Metilação de DNA , Regulação Neoplásica da Expressão Gênica/genética , Genes MDR/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Idoso , Idoso de 80 Anos ou mais , Apoptose/genética , Azacitidina/farmacologia , Sequência de Bases , Divisão Celular/genética , Ilhas de CpG/genética , Decitabina , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Genes MDR/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasias da Próstata/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
13.
Int J Urol ; 11(2): 119-21, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14706018

RESUMO

We report on a rare case of urinary silica calculi in a 10-month-old boy. The boy showed acute pyelonephritis with left hydronephrosis. Ultrasonography and computed tomography revealed a calculus at the left ureteropelvic junction and three additional calculi in the left renal pelvis. Because his acute pyelonephritis was refractory to conventional chemotherapy, the patient underwent successful left percutaneous nephrostomy followed by percutaneous nephrolithotripsy for the renal calculi. All stones disappeared and his postoperative course was uneventful. On infrared spectrophotometry, the wavelength pattern of the stones exhibited two peaks at 1100 and 1650 cm(-1), consistent with the determination that the calculi consisted of a mixture of silicate (78%) and calcium oxalate (22%). We consider that the etiology of the calculi in this child can be ascribed to the silicate-rich water used to dilute milk. In Japan, 46 adult patients with urinary silicate calculi have been reported in the literature; however, there is no report of the disease in an infant in Japan.


Assuntos
Cálculos Renais/diagnóstico por imagem , Cálculos Renais/terapia , Litotripsia/métodos , Nefrostomia Percutânea/métodos , Dióxido de Silício/química , Terapia Combinada , Seguimentos , Humanos , Lactente , Masculino , Medição de Risco , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Resultado do Tratamento
14.
Int J Urol ; 9(12): 717-8, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12492962

RESUMO

Intravesical thermometers are occasionally encountered in urologic practice. In the present paper, we describe the removal of a thermometer from the bladder of a woman who presented with irritable bladder symptoms. The thermometer was removed intact transurethrally using a rigid nephroscope and forceps, even though both ends of the thermometer were embedded in the bladder wall. Our retrieval technique may be of general use in such cases, and it should be attempted before resorting to open surgery.


Assuntos
Cistoscópios , Corpos Estranhos/terapia , Instrumentos Cirúrgicos , Bexiga Urinária , Adulto , Feminino , Humanos
15.
Infect Control Hosp Epidemiol ; 23(9): 506-10, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12269447

RESUMO

OBJECTIVE: To evaluate the usefulness of an assay using two polymerase chain reaction-based genotyping methods in the practical surveillance of methicillin-resistant Staphylococcus aureus (MRSA). METHODS: Nosocomial infection and colonization were surveyed monthly in a university hospital in Japan for 20 months. Genotyping with mec-HVR is based on the size of the mec-associated hypervariable region amplified by polymerase chain reaction. Toxin genotyping uses a multiplex polymerase chain reaction method to amplify eight staphylococcal toxin genes. RESULTS: Eight hundred nine MRSA isolates were classified into 49 genotypes. We observed differing prevalences of genotypes for different hospital wards, and could rapidly demonstrate the similarity of genotype for outbreak isolates. The incidence of genotype D: SEC/TSST1 was significantly higher in isolates causing nosocomial infections (49.5%; 48 of 97) than in nasal isolates (31.4%; 54 of 172) (P = .004), suggesting that this genotype may represent the nosocomial strains. CONCLUSION: The combined use of these two genotyping methods resulted in improved discriminatory ability and should be further investigated.


Assuntos
Toxinas Bacterianas/genética , Técnicas de Tipagem Bacteriana/métodos , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , DNA Bacteriano/genética , Resistência a Meticilina/genética , Reação em Cadeia da Polimerase/métodos , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Superantígenos , Técnicas de Tipagem Bacteriana/normas , Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Regiões Determinantes de Complementaridade/genética , Análise Discriminante , Surtos de Doenças/estatística & dados numéricos , Enterotoxinas/genética , Exfoliatinas/genética , Genótipo , Hospitais Universitários , Humanos , Incidência , Controle de Infecções/métodos , Japão/epidemiologia , Nariz/microbiologia , Reação em Cadeia da Polimerase/normas , Vigilância da População/métodos , Prevalência
17.
J Infect Chemother ; 5(3): 130-138, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11810504

RESUMO

Using the checkerboard titration method as well as the time-kill curve technique, we investigated the activities of beta-lactams, fluoroquinolones, amikacin, and fosfomycin alone and in combination against Pseudomonas aeruginosa isolated from patients with complicated urinary tract infections. In the checkerboard titration studies, none of 21 combinations demonstrated antagonism against 26 strains tested, and the mean fractional inhibitory concentration (FIC) indices for these combinations ranged between 0.4694 and 0.9828. Corresponding to the respective FIC indices, the bactericidal activity determined in combinations of meropenem with ciprofloxacin or amikacin and ceftazidime with ciprofloxacin at sub-minimum inhibitory concentrations (MICs) produced a great reduction in bacterial counts (>/=2 log10 CFU/ml) within 6 h of administration against most of the strains, including strains resistant to one or both drugs, and these synergistic effects were confirmed morphologically by scanning electron microscopy. In time-lag combinations, the first administration of ciprofloxacin or amikacin supplemented by meropenem with 1-h lag diminished bactericidal activity, in comparison with the simultaneous administration of the drugs. These results suggest that simultaneous combinations of beta-lactams with fluoroquinolones or amikacin may be useful alternatives for the treatment of serious infections due to P. aeruginosa.

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